Acalabrutinib for Waldenström Macroglobulinemia

Not currently recruiting at 45 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Acerta Pharma BV

Must not be taking: BCR inhibitors, BCL-2 inhibitors, Anticoagulants, PPIs

Disqualifiers: Prior malignancy, Cardiovascular disease, Autoimmune anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 28

Duration: Up to approximately 3.8 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of acalabrutinib for individuals with Waldenström Macroglobulinemia (WM), a rare blood cancer. The study examines the safety and efficacy of the drug for those who have either tried other treatments or are beginning treatment for the first time. It is open to individuals with WM who require treatment and have experienced frequent symptoms or cannot or prefer not to use chemotherapy. Participants must also be able to swallow capsules without difficulty. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications like immunotherapy within 4 weeks of starting, or anticoagulants like warfarin within 28 days of starting. You also cannot use proton-pump inhibitors during the trial.

Is there any evidence suggesting that acalabrutinib is likely to be safe for humans?

Research has shown that acalabrutinib is generally safe for people with Waldenström Macroglobulinemia (WM). One study found it to be very effective with few harmful side effects. Another study confirmed that acalabrutinib is easier on the body and has fewer side effects compared to other similar treatments. Although not yet approved specifically for WM, these findings strongly suggest that acalabrutinib is safe for people with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Waldenström Macroglobulinemia?

Acalabrutinib is unique because it targets the Bruton’s tyrosine kinase (BTK) pathway, which is crucial in the development and survival of cancer cells in Waldenström Macroglobulinemia. Unlike standard treatments like rituximab or chemotherapy, acalabrutinib specifically blocks BTK, potentially leading to fewer off-target effects and a more favorable side effect profile. Researchers are excited about acalabrutinib because it offers a more targeted approach, which could mean better outcomes and improved quality of life for patients with fewer side effects.

What evidence suggests that acalabrutinib might be an effective treatment for Waldenström Macroglobulinemia?

Research has shown that acalabrutinib effectively treats Waldenström Macroglobulinemia (WM). In this trial, participants will be divided into two groups: those previously treated and those who are treatment-naïve. One study found that 90.5% of previously treated patients saw their cancer respond to acalabrutinib. Another study reported that 93% of treatment-naïve patients also experienced a response, which is very encouraging. Acalabrutinib also has long-lasting effects, with 90% of patients maintaining their response for over 24 months. This suggests acalabrutinib could be a strong option for managing WM. ^{1 2 6 7 8}

Who Is on the Research Team?

AstraZeneca Clinical study Information Center

Principal Investigator

1-877-240-9479 [e-mail]

Are You a Good Fit for This Trial?

This trial is for adults with Waldenström Macroglobulinemia (WM), a type of blood cancer. It's open to those who haven't been treated before and want an alternative to chemoimmunotherapy, as well as patients whose WM has returned or didn't respond to at least one prior treatment. Participants must be able to swallow capsules and agree to use effective contraception if applicable.

Inclusion Criteria

I can swallow capsules without difficulty and can participate in all study procedures.

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)

I agree to use effective birth control during and 2 days after the study.

Exclusion Criteria

I do not have serious heart problems like recent heart attacks or severe heart failure.

I haven't had immunotherapy in the last 4 weeks.

I had cancer before, but it was either skin cancer treated successfully, cervical cancer that did not spread, or another type from which I've been free for 2+ years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib to evaluate safety, pharmacokinetics, pharmacodynamics, and activity in treating Waldenström Macroglobulinemia

Up to approximately 3.8 years

Cycle-based visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib (ACP-196)

Trial Overview The study is testing Acalabrutinib (ACP-196) for safety and effectiveness in treating WM. Researchers will look at how the body processes the drug, its impact on the disease, and any potential benefits it may offer.

How Is the Trial Designed?

Group I: Treatment Naïve Experimental Treatment 1 Intervention

Subjects with treatment-naïve Waldenström Macroglobulinemia. N=14

Group II: Previously Treated Experimental Treatment 1 Intervention

Subjects previously treated with Waldenström Macroglobulinemia N=92

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Published Research Related to This Trial

In a phase II study of tirabrutinib for Waldenström's macroglobulinemia involving 27 patients, 93% showed a major response, with high progression-free (92.6%) and overall survival (100%) rates at 24 months, indicating strong efficacy.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced grade 3-4 neutropenia and other adverse events, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year outcomes of tirabrutinib monotherapy in Waldenström's macroglobulinemia. Sekiguchi, N., Rai, S., Munakata, W., et al.[2022]

Acalabrutinib, a second-generation BTK inhibitor, has been shown to be more potent and selective than the first-in-class BTK inhibitor, ibrutinib, in treating B cell malignancies.

The review highlights the growing availability of targeted therapies for B cell cancers, emphasizing the potential of acalabrutinib based on preclinical and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. Wu, J., Zhang, M., Liu, D.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11672393/

Optimal use of BTK inhibitors in Waldenström's ... The long-term results of the study confirmed the high response rates (overall response rate (ORR) of 90.5% and major response rate (MRR) of 79.4 ...

2. ashpublications.org ashpublications.org/ashclinicalnews/news/3900/Acalabrutinib-Induces-Durable-Response-in-Patients

Acalabrutinib Induces Durable Response in Patients With ... Acalabrutinib Induces Durable Response in Patients With Waldenström Macroglobulinemia Available ; 24-Month Rate ; Duration of response, 90%, 84%.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302619302108

Acalabrutinib monotherapy in patients with Waldenström ... With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) ...

4. journals.lww.com journals.lww.com/hemasphere/fulltext/2022/06003/p1130__acalabrutinib_in_treatment_naive_or.1020.aspx

p1130: acalabrutinib in treatment-naive or relapsed ... Acalabrutinib is a highly effective treatment that achieved durable responses with a favorable safety profile in patients with TN or R/R WM.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02180724

NCT02180724 | An Open-label, Phase 2 Study of ACP-196 ... The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and activity of acalabrutinib in treating subjects with WM. Official ...

6. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30210-8/abstract

Acalabrutinib monotherapy in patients with Waldenström ... This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment- ...

7. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(18)30971-6/fulltext

Acalabrutinib in Patients (pts) with Waldenström ... Acalabrutinib is a highly effective treatment for WM with durable responses and limited toxicity. Funding source. Acerta Pharma, member of AstraZeneca Group ( ...

8. iwmf.com iwmf.com/wp-content/uploads/2023/09/BTK_frontline_Aug2023.pdf

BTK Inhibitors in the Frontline Management of Waldenstro¨ ... The safety and efficacy of acalabrutinib in patients with WM was investigated in a phase II study including 106 patients with WM, 92 R/R and 14 ...